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284 Cards in this Set
- Front
- Back
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Barone
Risk Factors for Gall Stones |
5Fs
Native Americans Birth Control |
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Barone
Most Important Risk of Gall Bladder Carcinoma? Clinical Signs? Likely Secondary progression |
Gallstones (Cholelithiasis)
Courvossier Sign Porcelain Gallbladder (Calcification) Liver Invasion |
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Couvossier Sign
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Enlarged palpable liver of Gallbladder Carcinoma
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Gallbladder with many yellow appearing stones
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Cholesterol Stones
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Gallbladder with black pigmented stones
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Bilirubinate Stones
Calcium Salts + Unconj Bilirubin |
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Causes of Pigmented GallBladder Stones?
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#1 Hemolytic Anemia
Bile Infection (Ascending Cholangitis) |
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Barone
Clinical Features of GallBladder Stones |
Usually Asymptomatic
RUQ w fatty meals *Biliary Colic* |
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Obstruction of Cystic Duct in Cholelithiasis?
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Biliary Colic
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Kaplan
Why is pregnancy a common cause of Gall Stones? |
Bile Stasis
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Kaplan
Gall Stone Elevated Calcium Radiopaque |
Pigment Stones
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Parasitic Causes of Gall Stones?
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Ascaris
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Kaplan
Pain Radiation of Gall Stones? Complications? |
R Shoulder, Tip of R Scapula
Cholecystitis, Pancreatitis, Cholangitis, *Gall Stone Ileus* |
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Cause of Gall Stone Ileus?
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Fistula Formation in essential
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Kaplan
Murphy's Sign? |
Pain on inspiration of Gall Bladder indicative of Cholecystitis
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Kaplan
Chronic Cholecystitis presentation |
Thickened wall
Calcium Deposits (Dystrophic Calcifications) --> Porcelain GB* |
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Kaplan
Porcelain GB? |
Sign of Chronic Cholecystitis which can predispose to Carcinoma
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Kaplan
Rotansky-Aschoff Sinuses? |
Invagination of mucosa into muscular layer in *Chronic Cholecystitis*
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Kaplan
Elderly patient **Palpable GallBladder** |
Think GB Cancer
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In the acinar liver model, which zone is closest to the vascular supply?
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Zone 1
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Where are the hepatic stellate cells found?
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In the Space of Disse, between the endothelial lining of the sinusoids and the hepatocytes
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Serum Measurements for Hepatocyte Integrity?
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^AST
^ALT ^LDH |
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Serum Measurements for Biliary excretory function? (+2 categories)
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-Serum Bilirubin (Total, Direct, Delta)
-Urine Bilirubin -Serum Bile Acids -Alkaline Phosphatase, GGT, 5'-nucleotidase from bile canaliculus damage |
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Serum Measurements of Hepatocyte Function? (+2 categories)
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1 - Serum Proteins - Albumin (decreased), PT time
2 - Hepatocyte Metabolism -Serum Ammonia, Aminopyrine Breath Test (decreased), Galactose Elimination (decreased) |
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What is the Aminopyrine Breath Test a measure of?
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Hepatic demethylation, decreased levels indicates decreased hepatic function
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What Factors are affected in a raised PT Time? Indication in Liver?
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5, 7, 10
Prothrombin, Fibrinogen decreased hepatocyte function |
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What capacity of liver function must be lost before hepatic failure ensues?
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80-90%
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Timelines -
Acute Liver Failure Fulminant Sub-fulminant Cause of Acute Liver Failure? |
Acute - 6mo + encephalopathy
Fulminant - 2 weeks + enceph + jaund Sub-Fulm - 3 mo + enceph+jaund Massive Hepatic Necrosis |
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Drugs which may trigger ALF?
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Acetaminophen*
Rifampin, Isonaizid (antimyco's) MOA inhibitors CCl4 Amanita Phalloides (Mushroom psn) |
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Which hepatitis rarely causes ALF?
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HCV
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Causes of Hepatic Dysfunction without necrosis?
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Tetracycline
Acute Fatty Liver of Pregnancy |
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Clinical Presentation and Mechanism of Ftor Hepaticus?
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Patient with Hepatic failure, "musty" or "sweet and sour" odor
Portosystemic shunting by mercaptan formation from methionine by GI bacteria |
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Presentation of hyperestrogenemia in Liver Failure?
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Palmar erythema and spider angiomas
hypogonadism and gynecomastia in males |
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Mechanism of Liver Failure Coagulopathy?
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Decreased clotting factors
GI Bleeds Reabsorbed blood into Liver Further Damage Cyclical |
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What is asterixis?
Best seen? Cause? |
Nonrhythmic rapid ext-flex movements of head and extremities
Best seen with arms in extension with dorsiflexed wrists hyperammonia of Liver Failure best |
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Clinical Signs of Hepatic Encephalopathy?
Morpholigic? |
Confusion, stupor, coma, death
Hyper-reflexia, rigidity, *Asterixis Astrocyte Swelling, brain edema |
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What is hepatorenal syndrome?
Major Abnormalities? Mechanism? Timeline? |
Renal failure in individuals with CHRONIC hepatic failure in absence of renal abnormalities
^Na, decr Urine output, elev creatinine and BUN Systemic Vasodilation --> Renal Vasoconstriction + ^Renal vasoactive mediators--> Decr GFT 2 weeks if aggrevated by infection or GI hemorrhage, 6 months if chronic |
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Chronic Liver Disease, Hypoxemia, and Intrapulmonary vascular dilations are characteristic of?
Causes? (+Key Mediator) Clinical Presentation? |
Hepatopulmonary Syndrome of Liver Failure
Vent-Perfusion mismatches, shunting of blood because of dilated vessels *NO* Orthodeoxia, Platypnea, Spider Nevi |
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Orthodeoxia?
Platypnea? |
Decreased oxygen saturation
Dyspnea relieved by lying down, worsened by standing *opposite of orthopnea* |
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Major Causes of Cirrhosis
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Alcoholism
Viral Hepatitis NASH Biliary Disease Iron overload |
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Three morphologic characteristics of Cirrhosis?
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Bridging Fibrous Septa
Parenchymal Nodules *DIFFUSENESS of previous two* |
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Cirrhosis -
Change in Collagen? Effect? |
Deposition of I/III in Space of Disse
Decreased capillarization Decreased exchange New portoportal and porto-central vein linkage Biliary Channel Destruction > Jaund |
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Mechanism of fibrosis in Cirrhosis?
Activation? Proliferation? Contraction? Fibrogenesis? Chemotaxis? |
Stellate to Myofibroblasts
Proliferation - PDGF, TNF Contraction - Endothelin-1 (ET-1) Fibrogenesis - TGF-B Chemotaxis - PDGF, MCP-1 |
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Causes of death in Cirrhosis? (3)
Major Clinical Consequences? (4) |
Progressive Liver Failure
Portal HT complications Hepatocellular Carcinoma Ascities, Splenomegaly, Portosystemic Shunts, Encephalopathy |
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1 -Prehepatic Portal HT?
2 - Hepatic Portal HT? 3 - Post? |
1 Thrombosis, Splenomegaly
2 Cirrhosis, Schistosomiasis, FattyChng, sacroidosis 3 rsHF, Restrictive Pericarditis, HepV obstruction |
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Pathophys of Portal HT?
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Increased Resistance - Stellate Cell Fibrosis, NO from endothelials
Increased Flow - Vasodilation of Splanchnics from increased NO due to high Bacterial DNA exposures from Portosystemic shunting |
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Characteristics of Ascities?
#1 Cause? If blood present ddx? |
>500mL serous fluid, >1.1g/dL serous:albumin ratio
85% by Cirrhosis If blood, disseminated intra-abdominal cancer |
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Mechanism of Ascities?
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1 - Sinusoidal HT --> Space of Disse --> Lymphatics, overcomes Thoracic Duct capacity
2 - Spanchnic Vasodilation - **Portal HT, Vasodilation, Sodium/Water retention |
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Shunts of Portal HT?
Most Dangerous? |
Rectum - hemorrhoids
Esophogastric Junction - Varicies Retroperineum Flaciform Ligament - caput medusae 40% of cirrhosis patients develop esophageal varicies |
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Origins of Bilirubin?
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RBCs 85%
Liver Hemoproteins (P450 cytochromes) 15% |
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Steps of Bilirubin Metab + Elim
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1 Heme to Biliverdin(heme oxygenase)
2 to Bilirubin (biliverdin reductase) 3 transport to liver on albumin 4 Uptake at sinusoidal membrane 5 UGT1A1 conj to bilirubin mono/di-glucuronides 6 Now water-soluble, excreted into bile 7 Deconj by B-glucuronidases to colorless urobilinogens in GI 8 20% reabs ileum/colon, some to urine |
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What does UGT1A1 stand for
What other functions does this family perform? |
UDP-glucuronyl-transferase
glucuronidation of steroids, carcinogens, and drugs |
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1 What are Bile Acids + Names?
2 How are Bile Salts formed? 3 Major Bile Acid function? Outcome? |
1 Bile Acids are major catabolic products of cholesterol
Cholic and Chenodeoxycholic Acid 2 Combination with Taurine or Glycine forms Bile Salts Bile Acids are detergents which water-solubilize hepaticly secreted lipids and solubilize dietary lipids for absorption 95% are reabsorbed |
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When does unbound unconj bilirubin inceased and what is the risk?
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Erythroblastosis fetalis, leading to Kernicterus via diffusion into the brain
Administration of protein-binding drugs |
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Bilirubin Delta Fraction?
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Binding of conjugated bilirubin to albumin in prolonged hyperbilirubinemia
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Why may a newborn have Jaundice?
What may exacerbate this? Serious disease that must be ddx'd? |
Hepatic conjugated material is immature for first 2 weeks
Breastfeeding, milk constains bilirubin deconj enzymes Kernicterus |
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Death <18 mo via Kernicterus
Colorless Bile High serum unconj bilirubin Diagonsis? Inheritance? Defect? Pathology? |
Crigler-Najjar 1
Autosomal Recessive absent UGT1A1 Liver normal on LM and EM |
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Patient with extreme Jaundice
Only monoglucurinated Bilirubin Present Diagnosis? Inheritance? Defect? Treatment? |
Crigler-Najjar 2
Autosomal Dominant Decreased UGT1A1 Phenobarbital causes hepatocellular ER hypertrophy |
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Mild fluctuating hyperbilirubinemia in absence of hemolysis or liver disease brought about by illness/exercise/fasting
Diagnosis? Inheritance + Mech? Secondary Effects? |
Gilbert Syndrome
Autsomonal Recessive, insertion reducing transcription Increased susceptibility to UGT1A1 metabolized drugs |
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Chronic and Recurrent Jaundice
Darkly Pigmented Liver Coarse pigmented granules in hepatocyte lysosomes Diagnosis? Bilirubin Values?Inheritance? Mechanism? Granules? |
Dubin-Johnson Syndrome
Chronically ^Conjugated Bilirubin Autosomal Recessive Defect in MRP-2 causes decreased release into bile canaliculi Granules are composed of epinephrine metabolites |
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Asymptomatic Jaundice
Morphologically normal Liver Defects into hepatocellular uptake and bilirubin excretion Diagnosis? Inheritance? Serum Values? |
Rotor Syndrome
Autosomal Recessive Elevated Conjugated Bilirubin |
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Where does bile accumulate in Cholestatis?
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Parenchyma
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1 Clinical Findings of Cholestatis?
2 Serum Values? 3 Morphologic Features of Hepatocytes and Portal Tracts? If untreated, outcome? |
1 Jaundice, *Pruritus*, Xanthomas, Malabsorption (A D K)
2 ^GGT, ^Alkaline Phosphatase 3 Hepatocytes - Feathery Degeneration, Bile Pigments, Bile Lakes Bile Duct Proliferation, Edema, Bile Pigmentation Leads of Portal Tract Fibrosis and Cirrhosis |
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Infantile Cholestatis with early Liver Failure
Severe Pruritus Normal GGT, no Bile Duct prolif No Cholangiocarcinoma |
Progressive Familiar Intrahepatic Cholestatis 1
ATP8B1 Gene |
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First Decade Cholestatis leading to cholangiocarcinoma with normal GGT values and absent bile duct prolif
pruritus, growth failure, cirrhosis |
PFIC 2
ABCB11 |
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Cholestatis with elevated GGT levels and unopposed bile salt detergent action on hepatocytes
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PFIC 3 with absent phosphatidylcholine
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Potential contact with HAV?
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Shellfish
Food industry workers Schools, Nurseries |
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Structure of HAV?
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27nm icosahedral nonenveloped +ssRNA of the picornavirus family
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1 When is a person with HAV contagious?
2 Incubation period? 3 Typical Disease? 4 Damage caused by? 5 Diagnosis? |
1 Shed feco-orally 2 weeks before and one week after Jaundice Presents
2 3-6 weeks 3 ACUTE, never Chronic 4 CD8+ 5 IgM rises with symptoms coincides with end of fecal shedding and declines in a few months |
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Location of HBV Chronic Carriers?
Age relation? |
Asia, Pacific Rim
Young more susceptible, lowest @adults |
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What is the structure of HBV?
Main HBs found in serum? |
42nm dsDNA spherical double-layered "Dane Particle"
Core is 28nm The small HBs (noninfectious) containing S only |
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Recovery from Chronic HBV Hepatitis is indicated by?
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Negative HBsAg
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HEALTHY Carrier HBV state is indicated by?
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+HBsAg >6months
-HBeAg +HBV DNA Normal AST and ALT |
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Vaccination strategy for HBV focuses on? When is this AB detectable?
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HBsAg forming Anti-HBs
Does not rise until acute disease has subsided for a few weeks to months |
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What signifies ACTIVE HBV replication?
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HBeAg, HBV DNA, DNA polymerase
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What suggests probable progression to infectivity and progression to chronic hepatitis in HBV?
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Persistent HBeAg levels
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Appearance of what AB in HBV implies acute infection is on the wane?
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anti-HBe
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1 When is a person with HAV contagious?
2 Incubation period? 3 Typical Disease? 4 Damage caused by? 5 Diagnosis? |
1 Shed feco-orally 2 weeks before and one week after Jaundice Presents
2 3-6 weeks 3 ACUTE, never Chronic 4 CD8+ 5 IgM rises with symptoms coincides with end of fecal shedding and declines in a few months |
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Location of HBV Chronic Carriers?
Age relation? |
Asia, Pacific Rim
Young more susceptible, lowest @adults |
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What is the structure of HBV?
Main HBs found in serum? |
42nm dsDNA spherical double-layered "Dane Particle"
Core is 28nm The small HBs (noninfectious) containing S only |
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What markers are present before the onset of HBV symtoms?
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HBsAg
IgM anti HBc ^ALT and AST |
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Recovery from Chronic HBV Hepatitis is indicated by?
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Negative HBsAg
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HEALTHY Carrier HBV state is indicated by?
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+HBsAg >6months
-HBeAg +HBV DNA Normal AST and ALT |
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Vaccination strategy for HBV focuses on? When is this AB detectable?
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HBsAg forming Anti-HBs
Does not rise until acute disease has subsided for a few weeks to months |
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What signifies ACTIVE HBV replication?
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HBeAg, HBV DNA, DNA polymerase
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What suggests probable progression to infectivity and progression to chronic hepatitis in HBV?
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Persistent HBeAg levels
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Appearance of what AB in HBV implies acute infection is on the wane?
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anti-HBe
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What do some mutated strains of HBV not produce despite being capable of replication?
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HBeAg
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HBV Vaccination?
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purified HBsAg from yeast
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Most Common Chronic Blood-Borne Infection?
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HCV
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Structure of HCV?
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small enveloped +ssRNA
Flaviviridae Family |
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Why is vaccination of HCV difficult?
Result? |
Genomic Instability via unstable NS5B (RNAdepRNApolym)
Antigenic Variability of E2 envelope protein Elevated titers of anti-HCV IgG do not confer immunity **REPEATED BOUTS** |
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Incubation period of HBV?
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Longest, 4-26 weeks
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Incubation period of HCV?
Detection of HCV RNA and HCV ABs in acute cases? |
6-12 (7-8) weeks
RNA detectable for only 1-3 weeks, ABs may be detectable or may not present for 3-6 weeks |
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Persistent Infection and Chronic Hepatitis are hallmarks of?
Resistance Mechanisms? (2) Serum Values? |
HCV
Genomic/Antigenic Variation **IFN inhibition persistently elevated HCV RNA despite antibodies, WAX/WANE Aminotransferases |
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What type of hepatitis is extremely rare with HCV?
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Fulminant
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HDV disease beginning 30-50 days following infection?
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Superinfection of HBV chronic carrier
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Phasic Characteristics of HDV Superinfection?
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1 - HDV infection, ALT increase, suppression of HBV
2 - HDV decreases, ALT fluctuation, HBV increase with development of **Cirrhosis and HCC** |
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In liver transplants what Hepatitis should you be suspicious of?
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HDV helper-independent
HDV viremia will only demonstrate if HBV breaks free of neutralization |
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Locations of HDV prevalence?
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Amazon, Africa, Middle East, Southern Italy
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HDV structure?
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35nm double shelled ssRNA similar to Dane Particle of HBV
smallest viral genome known |
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Serum values for Acute Coinfection HDV/HBV?
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+IgM-HBc and IgM-HDag
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Serum Values for HDV superinfection?
Treatment of HDV? |
+HBsAg (chronic infective marker)
IgM/G-HDag INF-a |
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1 HEV transmission?
2 Location / Susceptibility? 3 Presentation? 4 Structure? 5 Diagnosis? |
1 Zoonotic/Animal reservoirs enterically
2 INDIA, PREGNANT WOMEN 3 NEVER chronic 4 32-34nm unenveloped +ssRNA of Hepevirus genus 5 Simultaneous PCR of HEV RNA, ^serum aminotransferases, IgMHEV |
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Hepatitis virus resembling HCV which resides in bone marrow and spleen and is a common coinfector of HIV in contaminated blood
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HGV
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Which HVs do not cause Chronic?
Which causes Fulminant? |
HAV HEV
HBV |
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When are hepatitis viruses most infective?
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Later into asymptomatic phase, early into symptomatic phase
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Time definition of Chronic Hepatitis?
Most common Chronic symptom? |
6 Months
Fatigue |
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What type of Immune Diseases may Chronic Hepatitis lead to?
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Type 3 Hypersensitivities
Vasculitis, Glomerulonephritis |
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What type of Hepatitis ALWAYS requires medical attention if detected?
What is its treatment? |
HCV
Pegylated IFN-a and Ribavirin |
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Definition of HBV Healthy Carrier?
Who are healthy carriers? |
no HBeAg, anti-HBe present, normal aminotransferases, low or undetectable HBV DNA, no inflammation or necrosis
people who acquire the disease early (internationals) |
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"Ground-glass" hepatocytes with spheres and tubules of Ag forming a finely granular cytoplasm is unique to which hepatitis?
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Hepatitis B
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What differentiates the steatosis of HCV versus Toxic Hepatitis?
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HCV has FOCAL lobular regions of hepatocyte Macrovesicular streatosis
Toxic has PANLOBULAR micro+macrovesicular steatosis |
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How does Cholestatis present (in general and in hepatitis)?
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Bile Plugs in canaliculi
Brown pigmentation of hepatocytes |
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Hepatocyte injury in Acute Hepatitis?
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Ballooning Degeneration
Macrophage Aggregates Bridging Necrosis Apoptotic Cells Loss of Lobular Architecture |
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Kupffer Cells of Acute Hepatitis?
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Hypertrophic and hyperplastic with lipofuscin
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Interface Hepatitis of Acute Hep?
Effects on Canals of Hering? |
Periportal necrosis (from inflamm overflow from portal tracts)
Proliferation |
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Morphologic features of Chronic Hepatitis?
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Lymphoid Aggregates
Steatosis **Fibrous Tissue** Interface Hep Bridging Necrosis |
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What is Cryptogenic Cirrhosis?
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Cirrhosis without definitive cost, 20%
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Morphology of Cirrhosis? (Post-Hepatic?)
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Broad scarring, coarse irregularly nodular surface/structure
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HBV-induced Fulminant has?
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Massive apoptosis
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Shrunken, limp, Red liver
Wrinkled Capsule Necrosis + massive Hemorrhage Collapsed Reticulin network *Portal Tracts intact* |
Viral Fulminant Hepatitis
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Ductular Reaction?
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Oval cells of Canals of Hering undergo proliferation and differentiation and can completelely regenerate liver if damage is not too excessive
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Which Bacterias can directly invade the liver?
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S aureus (TSS)
S typhi (thyoid) T pallidum (2/3 syphilis) |
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Bacteria of Ascending Cholangitis?
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Reflects Gut Flora
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Which microbes most commonly cause liver abscess? (think developing countries)
Most common age? |
Echinococcal
Amebic Elderly |
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Microbe which commonly causes empyema / lung abscess secondary to liver abscess?
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Ameba
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Multiple small liver abscesses
Single Abscess Multiple purulent abscesses |
portal/systemic
trauma biliary |
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Liver Abscess with CYSTIC structure
with HOOKLETS, possible calcification outcome? |
Echinococcal
cysts ruptured and cause shock |
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Drugs related to Autoimmune Hepatitis?
Other causes? (3) |
Minocycline, Atorvastatin, Simvastatin, methyldopa, INFs, nitrofurantoin, pemoline, Black Cohosh
Regulatory T cell dysfunction Viral Other autoimmune disorders |
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Characteristic morphology feature of Autoimmune Hepatitis?
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Interface Hepatitis with PLASMA CELLS
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Serologic Findings in Autoimmune Hepatitis?
T1? |
Absence of Viral markers
Elevated IgG and g-Globulin high autoantibody titers T1 more common and systemic markers |
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Treatment of Autoimmune Hepatitis?
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Prednisone +/- Azathioprine
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MCC Fulminant Hepatitis?
MCC drug-induced ALF? |
Drug Reactions
Acetaminophen |
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Who is more susceptible to idiosyncratic drug reactions?
Definition? |
Adults
Women Drug reactions independent of dose |
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Common Drugs in Idiosyncratic Injury?
Chlorpromazine drug reaction? Halothane drug reaction? Methotrexate? |
Isonaizid, NSAIDs, anti-seizure meds
Cholestasis Immune-mediated Hepatitis Hepatic Steatosis and Fibrosis |
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Characteristic morphology of Reye Syndrome?
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Exensive microvesicular steatosis
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What must be done to diagnose Drug induced Hepatitis?
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Check Viral serological markers, both present identically
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Morphology of Hepatic Steatosis?
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Microvesicular --> macrovesicular
Fibrosis around Central Vein if chronic |
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Morphology of Alcoholic Hepatitis?
Fibrosis of Repeated bouts of heavy intake? |
Ballooning and Necrosis
Mallory Bodies + Neutrophils Fibrosis (Sinusoidal, Perivenular) Periportal fibrosis will predominate |
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Mallory Bodies?
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Eosinophilic Cytoplasmic Clumps within Hepatocytes
Commonly accompanied by Ns Surrounded by Fibrosis |
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Cirrhosis morphologic progression?
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"Hobnail" exterior appearance
Mixed Macro/Micro-nodular Loss of fat, shrunken "Laennec Cirrhosis" **Loss of Mallory Bodies** Bile Stasis |
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Laennec Cirrhosis?
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Tough Pale scar tissue of Cirrhosis formed by ischemic necrosis and fibrous obliteration
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Hobnail liver appearance?
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Prominent nodularity in cirrhosis from chronic regeneration and fibrosis
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Predispostions to Alcoholic Liver Disease?
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Women - estrogen ^s LPS fx @ liver
African Americans Asian - ALDH2 Co-morbidities - Iron, HBV, HCV |
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Cause of Hepatic Steatosis?
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^NADH+H
^lipid biosynthesis decreased lipoprotein secretion peripheral fat catabolism |
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Cause of Alcoholic Hepatitis?
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1 Acetaldehyde-adducts disrupt membrane function
Acetaldehyde Peroxidation 2 P450 ROS production 3 Decreased methionine metabolism > decreased glutathione metabolism > Oxidative Injury prone 4 CYP2E1 induction |
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Vascular effects of alcohol?
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Increases bacterial endotoxin release from Gut
->Stimulates Endothelins ->Activates Stellate Cells (PortalHT) |
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Serology of Fatty liver?
Alcoholic Hepatitis? Cirrhosis? |
mild ^bilirubin ^alkaline phosphatase
^Bili^AlkPhos*NeutroLeukocytosis ^ALT,^AST,hypoproteinemia, anemia |
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Kaplan
Risks for Physiologic Jaundice of Newborns? Treatment? |
Prematurity
Erythroblastosis Phototherapy |
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Kaplan
Key Feature of Dubin-Johnson? |
Black Liver
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Kaplan
Where does Alkaline Phosphatase originate? |
BILE CELLS
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Kaplan
Broad feature of Cirrhosis? MCC? Size division micro/macro? |
Regenerating Nodularity
Alcohol ><3mm |
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Kaplan
Why does Hyperestrogenemia in LF? |
Liver produces estrogen
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Kaplan
Kidney appearance in Hepatorenal Dysfunction? |
None
Renal Dysfunction in absence of structural damage |
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Kaplan
Earliest symptoms of Hepatitis? Icteric Phase? |
Weakness, Malaise, Fatigue
Dark Urine, Clay Colored Stools BOTH ^unconj/conj elevated, ALT/AST^ |
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Kaplan
Key morphologic features of Acute Hepatitis |
Lobular Disarray
Councilman Bodies (Apoptosis) Cholestatis Balloon Cells |
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Kaplan
Chronic Hepatitis - Types? Difference between persistent and Active? |
B,C, D
Persistent confined to portal tracts Active develops into parenchyma INTERFACE hepatitis Bridging --> Cirrhosis |
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Kaplan
Morphology associated with HBV carrier state? |
Ground-Glass appearance
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Kaplan
Key Feature of HEV? |
Severe in pregnant females
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Lab Diagnosis of HAV?
HBV? HCV? HDV? |
HAV - anti-HAV IgM
HBV - HBsAg, IgM-Hbc (HBeAg) HCV - ELISA anti-HCV, HCVRNA PCR HDV - IgM/G-HD, HDV RNA, HDag, |
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Kaplan
What is important about HBcAB? |
Present in Window Phase
while still capable of infecting, but no symptoms |
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Kaplan
What is important about HBeAg? |
Correlates with viral proliferation and infectivity
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HBV SEROLOGY
1 - Present in Acute? 2 - Prior Infection? 3 - Immunization? 4 - Chronic Infection? |
1-HBsAg HBeAg HBVDNA IgM-HBc
2 - IgG-HBc, IgG-HBs 3 - IgG-HBs 4 - HBsAg HBeAG HBVDNA, IgG-HBcAb -possibly IgM-HBc |
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Kaplan
Key Features Amebic Liver Abscess? |
Flask Shaped Ulcers
Blood in stools Necrotic Abscess of liver |
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Kaplan
Key Feature of Alcholic Hepatitis? |
Mallory Bodies - represent cytoskeletal aspects of hepatocytes
represents destruction WITHIN Cell (ddx viral) |
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Kaplan
Good DDX Alcoholic versus Viral Hepatitis? |
Fatty Change in Alcoholic
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RR
Type of Hyperbilirubinemia present in Viral Hepatitis? |
Combined
Defect in uptake, conjugation, and secretion |
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RR
MCC Jaundice? |
Viral Hepatitis
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RR
ALT to AST in Alcoholic Hepatitis? |
AST>ALT
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What indicates active HAV infection?
What indicated recovery/vaccination? |
IgM
IgG |
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Quanity limit differentiating nonalcohilc and alcoholic Fatty Liver?
|
20g/week
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What is NAFLD highly related to?
|
Obesity
Diabetes Insulin Resistance Hyperlipidemia Metabolic Syndrome |
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What is the pathogenesis of NAFLD?
|
Lipid peroxidation producing ROS
simultaneous lipid deposition and oxidative damage |
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Reliable diagnostic tool for NAFLD?
Serum Values? Common cause of death? |
Liver Biopsy
Elevated ALT/AST (ddx alcoholic) Cardiovascular Disease because of relation to metabolic disorders |
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Morphologic Characteristics of NASH?
|
*Steatosis*
Neutrophils, Mallory Bodies *Fibrosis* Fat droplets of predominantly TGs Ballooning Necrosis |
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Acquired Deposition of iron in tissues
|
Hemosiderosis
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What are the Characterizing Features of Hemochromatosis?
When does this diease present? Gender? |
Pigmented Cirrhosis (micronodular + hepatomegaly)
Skin Pigmentation DM ~Cardiac Dysfunction, Arthritis, *hypogonadism 50-60s, MEN |
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Hemochromatosis presents after __ grams of iron have accumulated
|
20
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___ and ___ cause Juvenile Hemochromatosis
Where is the more common found? |
HAMP and HJV
Liver heart SkM |
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___ is the most common cause of Adult Hemochromatosis followed by ___
|
HFE
TfR2 |
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___ mutation is found in 70-100% of Hereditary Hemochromatosis patients
Mechanism of defect? |
HFE
Cys->Tyr substitution (G-->A) leading to inactivation |
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How is excessive Iron toxic to tissues? (3)
|
Lipid Peroxidation
Activation of Stellate Cells (Fibrosis) ROS/Fe DNA damage (HCC) |
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In hemosiderosis, skin pigmentation results from increased __ ___ __
How does this appear? How can this be tested? |
melanin production
Slate-gray color Pruss Blue or Atomic Absorp Analysis |
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Morpholigic Presentation of Hemochromatosis in:
0 - Liver 1 - Pancreas 2 - Heart 3 - Joints 4 - Testes |
0 - Darkly Pigmented, micronodular cirrhosis, first @ periportal hepatocyte
1 - Deposit in Acinar+Islet Cells, Fibrosis 2 - Brown and Enlarged 3 - Acute Synovitis --> Pseudo-Gout 4 - nonpigmented, atrophic (reduced testosterone) |
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Hemochromatosis causes a 200x increase in risk of ___
|
HCC
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Neonatal Hemochromatosis is caused by _______ and is diagnosed by ______
|
In utero liver injury
Buccal Biopsy for hemosiderin deposits |
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MCCauses of Hemosiderosis?
|
Blood Disorders (^iron from transfusions and ^ absorption)
Alcoholism HBV/HCV Bantu Siderosis |
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In Wilson's Disease, most patients are ______ ______ with mutations on each _____ allele
What does this cause? (4) |
Compound Heterozygotes, ATP7B
Decreased incorp into Ceruloplasmin Decreased Bile excretion Inhibition of Ceruloplasmin-->Blood *Increased urinary copper |
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In the brain, Wilson's primarily affects the _____, which shows ____ and ____
How does this clinically present? |
Putamen, Atrophy/Cavitation
Parkinsonian like symptoms Behavior change frank psychosis |
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Green to breown deposits of copper in ______ membrane in the _____ of the _____
|
Kayser-Fleischer Rings
Desemet's, limbus, cornea |
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Serological diagnosis of Wilson's?
|
Decreased ceruloplasmin
Increased hepatic copper Increased Urine Copper **Serum copper of no value** |
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Treatment of Wilson's?
|
D-penicillamine or Trientine
Copper Chelators |
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What disease's distinctive feature is strongly PAS positive red circular granules of hepatocytes, especially in the portal tracts?
1 Where/What are these deposits? 2 What other symptoms are commonly seen? 3 What is seen in neonates? 4 Most common mutation? |
a1-antitrypsin deficiency
1 These are deposits of misfolded a1AT-Z in the ER 2 *Emphysema*, Wegners Granulomatous, Panniculitis, Anuerysms 3 Cholestasis (brown deposits also) 4 PiZZ |
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What is elevated in Neonatal Cholestasis?
|
conjugated bilirubin
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How is a differentiation between Neonatal Hepatitis (Neonatal Cholestasis) and Biliary Atresia made morphologically?
Why is this important? |
Hepatitis is primarily parenchymal with **GIANT CELLS** and lobular disarray while atresia has ductular effects
This is important because atresia patients should undergo immediate surgergy |
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Secondary Biliary Cirrhosis
1 - Etiology 2 - Predilection 3 - CS 4 - Lab 5 - Path/Morpho |
1 - Extrahepatic Bile Duct Obstructions - #1 Gallstones, Atresia, Pancreatic Carcinoma
2 - 3 - Pruritus, Jaundice, Malaise, Dark Urine, Light Stool, HepSplenMega 4 - ^bili/ALP, Bile Acids, Chol 5 - Green granular, jigsaw fibrous septae, Bile Stasis, Bile Duct proliferation, *Neutrophils*, Portal Tract Edema |
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Why are neutrophils present in SBC?
|
Inflammation and possible ascending cholangitis (coliforms, enterococci)
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PBC
1 - Etiology 2 - Predilection 3 - CS 4 - Lab 5 - Path/Morpho |
1 - Autoimmune
2 - WOMEN 3 - Xanthenlasmas, Hepatomegaly, Melanin hyperpigmentation, pruritus, malaise, steatorrhea, vitD deficiency 4 - ^ALP/Chol/Bili, **Automitochondrial ABs to PDH complex 5 - Lymphocytic Portal Tract Infiltration, noncaseating granulomas, intrahepatic duct fibrosis and cirrhosis |
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PBC patients have an increased risk of _____?
Major cause of death? Extrahepatic relations? |
HCC
Liver Failure --> variceal hemorrhage + infection Autoimmune diseases (Sicca) |
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Treatment of PBC?
|
Ursodeoxycholic Acid
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"Beading" of contrast medium of intrahepatic and extrahepatic bile ducts is characteristic of?
What is this strongly correlated to? |
PSC
Ulcerative Cholitis |
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___ is a disorder of the bile ducts with lymphocytic inflitrate, intermittent *onion-skin fibrosis* and inflammation
____ is found in 80% of these patients Predisposition to? |
PSC Primary Sclerosing Cholangitis
atypical p-ANCA (also anti-SmAB, ANAs, RF) Cholangiocarcinoma, HCC, Chronic Pancreatitis |
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What can be used for pruritus?
|
Cholestryamine
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The group of diseases causing altered architecture of the biliary tree commonly present with?
name them |
Hepatosplenomegaly and Portal HT without hepatic dysfunction in childhood or adolescence
VonMeyenburg, PCLD, CongHepFibr, Caroli, Alagille |
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Small clusters of modestly dilated bile ducts embedded in a fibrous stroma peri-portal tracts
dilated and irregulary shaped bile ducts |
Von Meyenburg "Bile Duct Hamartomas"
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Enlarged irregular portal tracts with broad bands of collagenous fibrosis dividing the liver into islands
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Congenital Hepatic Fibrosis
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Segmentally dilated intrahepatic large bile ducts with inspissated bile, frequently complicated by infections and stones
|
Caroli Disease
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________ is highly associated with the autosomal recessive form of Polycystic kidney disease (PKHD1)
|
Congenital Hepatic Fibrosis
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_____ is a rare multiorgan disorder characterized by the absence of bile ducts
Cause? 5 Major Clinical Features? |
Alagille
Jagged1 mutations on c20 Chronic Cholestasis, Peripheral stenosis of PA, Butterfly-like vertebral arch defects, Posterior embryotoxon, hypertelic facies |
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Interruption of which segment of the hepatic artery causes focal infarction? which does not?
|
Intrahepatic will, main will not unless liver transplant
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Sharply demarcated areas of red-blue discoloration follow acute thrombosis of what hepatic blood supply? Name?
|
Intrahepatic Portal Veins
Infarct of Zahn |
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Clinical Presentation of Impaired hepatic blood inflow?
Causes? |
Esophageal Varicies
Splenomegaly Intestinal Congestion NO Ascities Hepatic Artery / Portal Vein compromise Portal Fibrosis or HT |
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What are some causes of Portal Vein Obstruction?
|
Sepsis --> pylephlebitis of splanch circ
Hypercoagulabilitiy Trauma Pancreatitis/Cancer HCC Cirrhosis |
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______ is common in India, presenting with upper GI bleeds, and causes impaired hepatic blood flow
|
Noncirrhotic Portal Fibrosis
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______ is found in Japanesse women, presents with splenomegaly, and causes decreased hepatic blood flow
|
Idiopathic Portal Hypertension
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What are some causes of impaired intrahepatic blood flow?
|
Cirrhosis
Sickle Cell DIC Eclampsia Metathesis Passive Congestion (rsHF) and Centrilobular Necrosis (lsHF) |
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Presentation of impaired intrahepatic blood flow?
|
Ascities
Esophageal Varicies Hepatomegaly ^aminotransferases |
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Sinusoidal dilation leading to blood-filled cystic spaces of the liver
Related to? |
Peliosis Hepatis
Bartonella, AIDs, cancer, TB, steroids, danazole, oral contraceptives |
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What type of Hepatic Circulatory are the following findings related to, what are some causes?
Ascities Esophageal Varicies Hepatomegaly ^aminotransferases |
Impaired intrahepatic
Cirrhosis, Systemic Circulatory Compromise, Peliosis Hepatis |
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Obstruction of two or more major hepatic veins producing liver enlargement, pain, and ascities
How does this present? |
Budd-Chiari Syndrome
extreme blood retention in the liver (Ascities, hepatomegaly, Jaundice, ^aminotransferases) |
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What are some causes of Hepatic Vein Thrombosis? (Budd-Chiari)
|
Coag disorders
Pregnancy HCC Antiphospholipid syndrome |
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Treatment of Acute Hepatic Vein Thrombosis?
|
Mortality unless portosystemic venous shunt is made
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Onset of Ascities, hepatomegaly, ^aminotransferases, Jaundice following Allogenic Bone marrow transplant or chemotherapy should raised suspicion of what Hepatic Outflow obstruction disorder?
What is the mechanism? |
Sinusoidal Obstruction syndrome
Subendothelial swelling and finely reticular collagen resulting from toxic effects on endothelial lining |
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What is the result of an Acute Graft versus Host reaction in the liver?
|
Necrosis of hepatocytes and bile duct cells with parenchymal and portal tract inflammation
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In Chronic Hepatic Graft versus host, portal vein and hepatic vein radicules may show ______, a process in which a subendothelial lymphocytic infiltrate lifts the endothelium from its BM
|
Endothelitis
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What is the morphology of Acute Liver transplant rejection?
|
Mixed inflammatory cell infiltration wit EOSINOPHILS and endothelitis
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MCC Jaundice in prego?
Most dangerous? |
Viral Hepatitis
HEV |
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|
What differentiates Eclampsia and preeclampsia
|
Hyper-reflexia and seizures
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What are the components of the HELLP syndrome?
|
Hemolysis
Elevated Liver enzymes Low Platelets |
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What are the characteristics of eclampsia?
|
HT, proteinuria, peripheral edema, coag aborms, DIC
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What is the morphology of Eclampsia/Pre?
|
normally sized firm and pale liver with small red patches of hemorrhage
periportal fibrosing hemorrhagic necrosis Subcapsular Hematomas under Glisson's capsule |
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When does AFLP present?
|
Third Trimester
|
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What is the presentation, morphology, and cause of AFLP?
|
Bleeding/N/V/Jaundice in 3rd trimester
Microvesicular fatty transformation 3-hydroxyacyl toxicity |
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_____ presents with pruritus, dark urine, light stools, and jandice in the third trimester of pregnancy
|
Intrahepatic Cholestatis of Pregnancy
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What is the common factor in causing focal nodular hyperplasia and nodular regenerative hyperplasia?
|
Focal or diffuse alternations in hepatic blood supply
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Following use of steroids or oral contraceptives the finding of a small nodule with a gray-white depressed *Stellate scar center containing vasculature and radiating septae containing lymphocytic infiltrates and thickened plates
|
Focal Nodular Hyperplasia
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A liver entirely transformed into roughly spherical nodules in the absence of fibrosis is _____
What is required to visualize this? Who is at risk? |
Nodular Regenerative Hyperplasia
Reticulin Staining HIV-infected persons, organ transplants |
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|
Discrete red-blue soft nodules <2cm located directly beneath the liver capsule composed of vascular channels in a fibrous stroma
|
Cavernous Hemangiomas
|
|
|
Neoplasms of young women which regress when oral contraceptives are discontinued
|
Hepatic Adenomas
|
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|
When are hepatic adenomas prone to develop into cancer?
|
1 mutations of B-catenin gene
2 glycogen storage diseases |
|
|
Pale yellow bile-stained nodules often found beneath the hepatic capsule resembling normal hepatic structure with steatosis and *absent portal tracts*
|
Hepatic Adenoma
|
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MCCs of Angiosarcomas?
|
Vinyl Chloride
Arsenic Thorotrast |
|
|
Liver tumor of young child composed of small polygonal fetal cells forming acini/tubules/papillary structures
Characteristic (genetic) feature? Associations? Other form possible? |
Epithelial type Hepatoblastoma
WNT/B-catenin pathway activation Familiar Adenomatous Polyposis Syndrome and Beckwith-Wiedmann Syndrome Mesenchymal type |
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|
82% of HCC cases are associated with?
Four major etiologic factors? |
chronic HBV
Viral Hepatitis NASH Alcoholism Aflatoxins |
|
|
What is the difference in HCC of endemic areas versus western?
|
Westerners get disease later, cirrhosis MUCH more prevalent and is not as strongly correlated to HBV
|
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|
Aflatoxin, produced by _________ in contaiminated ___ and ____s causes HCC by mutations of ___
|
Aspergillus flavus
Peanuts and grains p53 |
|
|
Pale to slightly green nodules of the liver with high propensity to invade vasculature
|
HCC
|
|
|
Single large hard "scirrhous" eosinophilic neoplasm with dense collagen bundles (fibrous bands) in person aged 20 - 40 with no underlying Chronic Liver disease
|
Fibrolamellar Carcinoma
|
|
|
Differentiation between cirrhosis and HCC on physical exam? Serologically?
Most valuble for diagnosis? |
HCC is more irregular/nodular
elevated serum a-FP Imaging studies |
|
|
Most common site of HCC metathesis?
Most common causes of death (4) Treatment to prolong life? |
Lungs
Cachexia, Varicies, Liver Failure Coma, Rupture-->hemorrhage Sorafenib a kinase inhibitor |
|
|
Most common ethnicity for CCA?
Predispositions? |
Hispanics
PSC Caroli Diease Choledochal Cysts HCV Throtrast *Opisthorchis sinesis in Asia* |
|
|
Firm gray nodules of the bile duct wall with squamous features and abundant fibrous stroma
Most common site? |
Extrahepatic Cholangiosarcoma
Junction of R/L Hepatic Ducts = *Klatskin Tumors* |
|
|
Firm and Gritty desmoplastic (dense collagenous stroma) sclerosing adenocarcinoma of the liver with either a tree-like or massive growth appearance
|
Intrahepatic Cholangiosarcoma
|
|
|
What cells are related to HCC-CCA tumors?
|
Oval Cells
|
|
|
What is present in 20-100% of Cholangiosarcomas?
|
KRAS
|
|
|
What tumors are most likely to deposit in the liver?
How are they detected and what is their normal progress? |
Colon, Breast, Lung, Pancreas
Palpation of hepatomegaly with a nodular border Outgrow their blood supply developing a central necrosis |
|
|
Folding of the gall bladder fundus is termed?
|
Phrygian cap
Most common anomaly of GB |
|
|
In western cultures, over 90% of gallstones are _____ stones, composed of over 50%
|
Cholesterol
cholesterol monohydrate |
|
|
What is the mechanism of estrogen's effect of producing gallstones?
|
Increased cholesterol uptake and synthesis from increased HMG-CoA reductase and lipoprotein receptor activity
|
|
|
Hepatic Genetic Factor predisposing to cholesterol gallstones?
|
D19H variant of ABCG5
|
|
|
Four Simultaneous factors of Cholesterol Stone formation?
|
1 - Supersaturation
2 - Hypomobility 3 - Nucleation 4 - Accretion (mucus hypersecretion) |
|
|
Infection of the biliary tree with _____(3) increases the risk of Pigmented Gallstones
Why? |
E coli
O sinensis Ascaris lumbricoides Increased activity of B-glucuronidases leads to deconj |
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|
___ pigment stones are typically found in the sterile gallbladder and are radiopaque
|
Black
|
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____ pigment stones are typically found in the infected intrahepatic or extrahepatic ducts and are radiolucent
|
Brown
|
|
|
Inflammation of the Biliary Tree
|
Cholangitis
|
|
|
______ occurs when a large gallstone erodes directly into an adjacent loop of small bowel
|
Bouveret's Syndrome (Gallstone Ileus)
|
|
|
Inflammation of the Gallbladder
|
Cholecystitis
|
|
|
Acute _____ Cholecystitis occurs with obstruction in the absence of infection.
Mechansim of damage? |
Calculous
disruption of protective glycoprotein layer by toxic lysolecithins, allowing detergent action |
|
|
Acute _____ Cholecystitis occurs without obstruction and is caused by ischemia
Causes? |
Acalculous
Immunosuppresion Trauma DM Infection Hypotension |
|
|
____ is a purely pus exudate in acute cholecystitis
Causes? |
Empyema of the GB
Clostridia Coliforms (Gas producing organisms) |
|
|
Which (calculous/acalculous) Acute Cholecystitis more commonly results in Gangreneous / perforation? Why?
|
Acalculous, symptoms are more insidious
|
|
|
What bacterial agents can cause a primary acute acalculous cholecystitis
|
S aureus
S typhi |
|
|
Outpouching of the mucusal epithelium in Chronic Cholecystitis
|
Rokitansky-Aschoff Sinus
|
|
|
Extensive dystrophic calcification within the GB?
Cause? Risk? |
Porcelain Gallbladder
Chronic Cholecystitis Cancer |
|
|
Shrunken gallbladder with a massively thickened hemorrhagically necrotic nodular wall
|
Xanthogranulomatous Cholecystitis
|
|
|
Atrophic, chronically obstructed gallbladder with only clear secretions
|
Hydrops of the Gall Bladder
|
|
|
Infection of the intrahepatic biliary radicles
MCCs? |
Ascending Cholangitis
E coli, Kleb, Interococcus, Enterobacter, Clostridium, Bacteriodes |
|
|
_____ Biliary Atresia is most commonly seen with extrahepatic defects of organ development
|
Fetal
|
|
|
____ Biliary Atresia is seen in the absence of other structures anomalies
Causes? |
Perinatal
Reovirus Rotavirus CMV |
|
|
When is Biliary Atresia Treatable? What is this Treatment?
|
Type 1/2, if doesn't go above porta hepatis
Kasai |
|
|
Congenital dilations of the common bile duct typically before the age of 10
Commonly associated with? |
Choledochal Cysts
Caroli Disease |
|
|
_____ is a hyperplasia of the gall bladder muscle layer with hyperplastic glands
|
Adenomyosis
|
|
|
MCC of Gall Bladder Cancer?
|
Gall Stones, 95% of cases
|
|
|
Poorly defined areas of diffuse thickening and induration of the gallbladder with scirrhous consistency
|
Infiltrating Gall Bladder Cancer
|
